Treatment with Apocynin Limits the Development of Acute Graft-versus-Host Disease in Mice

• Published in: Journal of Immunology Research Vol. 2019; no. 2019; pp. 1 - 14
• Main Authors: Pinho, Vanessa, Teixeira, Mauro Martins, Martins, Débora Gonzaga, Ávila, Thiago Vinicius, Athayde, Rayssa Maciel, de Resende, Carolina Braga, Gonçalves, William Antonio, Bernardes, Priscila T. T., Rezende, Barbara Maximino, Castor, Marina G. M.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 2019; Hindawi; Hindawi Limited; Wiley
• Subjects: Acetophenones - pharmacology; Animals; Aprotinin; Atherosclerosis; Bone marrow; Bone marrow transplantation; Chemokines; Chimerism; Cytokines; Cytokines - metabolism; Disease; EDTA; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - metabolism; Graft vs Host Disease - mortality; Graft-versus-host reaction; Grafting; Health aspects; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic stem cells; Immunology; Immunosuppressive Agents - pharmacology; Inflammation; Inflammatory response; Intestine; Leukocyte migration; Liver - immunology; Liver - metabolism; Liver - pathology; Lymphocytes; Macrophages - metabolism; Mice; Mortality; NAD(P)H oxidase; NADPH Oxidases; Organs; Oxidase; Oxidases; Oxidative Stress; Pathogenesis; Reactive oxygen species; Reactive Oxygen Species - metabolism; Stem cell transplantation; Stem cells; Translocation; Transplantation; Transplantation Chimera; Transplantation, Homologous; Transplants & implants; Brazil; Japan
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2019/9015292

Graft-versus-host disease (GVHD) is the most serious complication limiting the clinical utility of allogeneic hematopoietic stem cell transplantation (HSCT), in which lymphocytes of donors (graft) are activated in response to the host antigen. This disease is associated with increased inflammatory response through the release of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS). In this study, we have evaluated the role of ROS in GVHD pathogenesis by treatment of recipient mice with apocynin (apo), an inhibitor of intracellular translocation of cytosolic components of NADPH oxidase complex. The pharmacological blockade of NADPH oxidase resulted in prolonged survival and reduced GVHD clinical score. This reduction in GVHD was associated with reduced levels of ROS and TBARS in target organs of GVHD in apocynin-treated mice at the onset of the mortality phase. These results correlated with reduced intestinal and liver injuries and decreased levels of proinflammatory cytokines and chemokines. Mechanistically, pharmacological blockade of the NADPH oxidase was associated with inhibition of recruitment and accumulation of leukocytes in the target organs. Additionally, the chimerism remained unaffected after treatment with apocynin. Our study demonstrates that ROS plays an important role in mediating GVHD, suggesting that strategies aimed at blocking ROS production may be useful as an adjuvant therapy in patients subjected to bone marrow transplantation.